芹菜素逆转肺癌A549/DDP细胞耐药及机制  

The effect and mechanism of apigenin reverse drugs resistance on A549/DDP cells

作　　者：赵亚新[1] 刘洁凡[2] 钱海鑫[1] 

机构地区：[1]苏州大学附属第一医院普外科,江苏苏州215006 [2]温州医科大学附属第一医院全科医学肿瘤康复科,浙江温州325000

出　　处：《南京医科大学学报（自然科学版）》2017年第11期1385-1388,1394,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：温州市科技局项目(Y20160403;Y20100257);浙江省中医药管理局项目(2009YB024)

摘　　要：目的 :研究芹菜素对肺癌A549/DDP细胞的作用,探讨芹菜素逆转肺癌耐药的作用及机制。方法 :体外培养肿瘤细胞,以不同浓度芹菜素作用为实验组,用MTT法检测A549/DDP细胞增殖和分析药物敏感性,用Rhodamine-123潴留实验检测A549/DDP细胞内药物外排情况,用Western blot法检测肿瘤细胞内P-糖蛋白(P-glycoprotein,P-gp)和肺耐药蛋白(lung resistance-related protein,LRP)表达情况,用RT-PCR法检测肿瘤细胞内多药耐药基因(multidrug resistance gene l,MDR1)m RNA和LRP m RNA的转录情况。结果 :与DDP组相比,20、40、80μmol/L的芹菜素明显抑制了A549/DDP细胞生长增殖(P<0.05)。DDP对A549/DDP细胞的IC50为(14.33±0.41)μg/m L,在芹菜素作用下其IC50降为(5.76±0.36)μg/m L,逆转倍数为2.48,两者相比有统计学差异(P<0.05)。芹菜素作用下,A549/DDP细胞内的Rhodamine-123蓄积增加,细胞内P-gp表达减弱,MDR1 m RNA转录水平下降,对LRP表达及LRP m RNA转录无明显改变。结论:芹菜素对A549/DDP细胞生长有抑制作用;芹菜素还具有逆转A549/DDP细胞肿瘤耐药的功能,其机制与降低MDR1 m RNA转录和下调P-gp介导的药物外转功能有关。Objective：To study the effect of apigenin on A549/DDP cells,and to explore the effect and mechanism of apigenin re- verse drugs resistance on A549/DDP cells. Methods： The cells were cultured with different concentrations apigenin. A549/DDP cells proliferation and drug sensitivity was detected by MIT asssy. The drug extracellular transport was detected by Rhodamine-123 reten- tion experiment, the P-gp and the LRP expression in the tumor cells was detected by Western blot, and the transcription of MDR1 mRNA and LRP mRNA in the tumor cells was detected by RT-PCR. Results： The apigenin can inhibit the A549/DDP cells prolifera- tion. There were significant differences between the apigenin groups（20,40,80 Ixmol/L） and the DDP group（P〈0.05）. The DDP＇s ICso with the apigenin was （5.76-＋0.36） p^g/mL in A549/DDP cells. The DDP＇s ICso without the apigenin was （14.33＋-0.41）p^g/mL in A549/ DDP cells, and the reversal index was 2.48. The apigenin can make high Rhodamine-123 accumulate in A549/DDP cells, down-regu- late the P-gp expression in A549/DDP cells, and decrease the transcription of MDR1 mRNA in A549/DDP cells. Conclusion： The apigenin may inhibit the A549/DDP cells proliferation and to reverse drug resistance in A549/DDP cells, and the mechanism was ralated to decrease the MDR1 mRNA transcription and down-regulate the expression of P-gp that mediated drug extracellular trans- port.

关 键 词：芹菜素 肺癌 多药耐药 逆转 

分 类 号：R734.2[医药卫生—肿瘤]